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T cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) — an update on emerging negative immune checkpoints in cancer treatment
Full text linkImmunotherapy is currently one of the most important treatment options for patients with various cancers. It is predominantly based on immune checkpoint inhibitors (ICIs), which are supposed to reverse immune suppression caused by interactions of negative immune checkpoints with their ligands. Cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand, programmed death ligand 1 (PD-L1) are the checkpoints targeted by antibodies registered in various types of cancer to enable effective anti-cancer immune response. Despite numerous possibilities, other molecules belonging to immune checkpoints — T cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), are being extensively researched, mainly due to their role in cancer progression and resistance to immunotherapy. Recently, the first antibody against LAG-3 — relatlimab has been registered in melanoma, and many others are tested in the final stages of clinical trials. Thus, understanding their intricate functions and developing strategies to use them can create opportunities to apply immunotherapy in cancer treatment. This article describes their characteristics and potential role in solid-tumor treatment with TIM-3, LAG-3, and TIGIT molecules, which have been connected to tumor progression, poor survival, and poor prognosis in many tumor types.
Progressive respiratory failure in a patient with wood dust exposure — a case report with an unexpected outcome of adenocarcinoma with ALK gene rearrangement
Full text linkLung cancer remains the leading cause of cancer-related deaths among both men and women in Poland. There are various types of lung cancer, with non-small cell lung cancer (NSCLC) being the most prevalent. Within NSCLC, adenocarcinoma is the most common subtype. Lung adenocarcinoma poses significant challenges in effective treatment due to its complex molecular profile. Recently, significant advancements have been observed in targeted therapies for lung cancer, which are based on the molecular diagnosis of cancer subtypes. Patients with adenocarcinoma with ALK gene rearrangements have the possibility of effective therapy with ALK inhibitors, especially the third generation of these drugs — lorlatinib. Here, a 39-year-old male admitted to the documented clinic with symptoms of respiratory failure is presented. He had a long-term history of employment in the wood industry. The course of the disease was rapid and it did not allow for diagnosis and treatment before the patient’s death. In the autopsy material pneumonic type of lung adenocarcinoma (PLADC) was diagnosed, and immunohistochemical method revealed expression of aberrant ALK protein. This case report is the first according to the literature in which ALK gene rearrangement was found in a non-smoking, young patient exposed to wood dust
Use of ruxolitinib in a patient with polycythemia vera and severe pruritus
No full textŚwiąd to objaw znacząco obniżający jakość życia części pacjentów z czerwienicą prawdziwą (PV, polycythemia vera). Jego złagodzenie często nastręcza wiele trudności. Zastosowanie ruksolitynibu może prowadzić do szybkiego zmniejszenia, a nawet całkowitego ustąpienia świądu. Lek ten ma również potencjał modyfikowania długofalowego przebiegu PV.Pruritus is a symptom that significantly reduces the quality of life in some patients with polycythemia vera (PV). Its relief is often challenging. Treatment with ruxolitinib can lead to a rapid reduction or even complete resolution of itching. This medication may also contribute to modifying the long-term course of the disease
Zastosowanie połączenia dipropionianu betametazonu z kwasem salicylowym w leczeniu dermatoz zapalnych
No full textPreparaty łączone są powszechnie stosowane w leczeniu miejscowym wielu dermatoz zapalnych. Jednoczesne zastosowanie dwóch substancji o różnych mechanizmach działania może spowodować efekt addycyjny, zwiększając tym samym skuteczność pojedynczych substancji, jeśli każda z nich stosowana jest oddzielnie. Miejscowe glikokortykosteroidy stanowią fundament procesu terapeutycznego wielu schorzeń dermatologicznych o podłożu zapalnym, autoimmunologicznym, alergicznym bądź przebiegających z nadmierną proliferacją naskórka. Dipropionian betametazonu jest silnym agonistą receptora glikokortykosteroidowego, zaliczanym do klasy III według klasyfikacji Światowej Organizacji Zdrowia (WHO, World Health Organization). Kwas salicylowy cechuje się właściwościami keratolitycznymi, przeciwzapalnymi, a także stymulującymi proces regeneracji. Eksfoliacja keratynocytów z lokalizacji objętych hiperkeratozą, uzyskana z pomocą kwasu salicylowego, sprzyja penetracji substancji aktywnych w głąb skóry, bezpośrednio do ognisk chorobowych. Aplikacja preparatu łączonego, który zawiera zarówno dipropionian betametazonu, jak i kwas salicylowy, zwiększa tym samym skuteczność farmakoterapii wielu dermatoz zapalnych, ze szczególnym uwzględnieniem schorzeń dermatologicznych przebiegających z hiperproliferacją i nadmiernym rogowaceniem naskórka
Anatomical observation of phrenic nerve branch variations at the cervicothoracic junction and upper mediastinum: two case reports
No full textBackground: The authors report phrenic nerve branch and communication variations at the cervicothoracic junction and upper mediastinum through adult cadaveric dissection, analyze their local morphological characteristics, and discuss their anatomical significance in conjunction with previous literature. Materials and methods: During adult cadaveric dissection, two cases of phrenic nerve anatomical variations were discovered. Results: Case 1 showed the left phrenic nerve composed of upper and lower branches that straddled the transverse cervical artery at the C4 level before reuniting and entering the thoracic cavity, with subsequent mediastinal course and terminal distribution consistent with standard anatomical descriptions. Case 2 showed early branching of the left phrenic nerve within the upper mediastinum, with its superior and inferior branches connected by communicating branches before joining the vagus nerve, while the main phrenic nerve trunk continued along its typical path to terminate at the diaphragm. Both variations were primarily limited to proximal branches or communicating structures, without significantly altering the main trunk course of the phrenic nerve within the mediastinum. Conclusions: This study reports two types of branch and communication variations of the phrenic nerve at the cervicothoracic junction and upper mediastinum. However, the main trunk course within the mediastinum and terminal distribution at the diaphragm remained relatively constant overall. Understanding these variations helps enrich phrenic nerve anatomical data and provides anatomical basis for identification and protection of the phrenic nerve during related cervical, mediastinal, and minimally invasive surgeries
Complex accessory tendon anatomy of the pes anserinus: a unique combination of accessory tendons in a right knee
No full textBackground: The pes anserinus (PA) is a tendinous complex located on the anteromedial surface of the proximal tibia, formed by the conjoined insertions of the sartorius, gracilis, and semitendinosus muscles. It contributes to internal rotation and flexion of the tibia, providing stability to the medial knee compartment.
Case report: During the routine dissection of a 75-year-old female cadaver, an unusual PA variant was found. On the right limb, four accessory tendons were identified: one accessory sartorius tendon (aSART), one accessory gracilis tendon(aGRT), and two accessory semitendinosus tendons (aSTT1 and aSTT2). Distally, the aSTT1 fused with the aGRT and subsequently joined the aSART, forming a single fascial band that inserted slightly inferior to the typical PA footprint. No corresponding variations were present on the contralateral side. The coexistence of accessory slips from all three PA muscles appears exceedingly rare.
Conclusions: This case report presents a unique variant of PA, emphasizing the extent of its anatomic variability. Awareness and recognizing such variants of PA is crucial for surgeons, as this knowledge may help prevent the misidentification of tendons during medial knee procedures and tendon graft harvesting
Effects of blue light exposure on human skin at the molecular, cellular, and clinical levels: A systematic review
No full textBackground: High-energy visible (HEV) blue light (400–500 nm) is increasingly recognized as a contributor to skin damage beyond ultraviolet (UV) radiation. Evidence links HEV exposure to oxidative stress, extracellular matrix degradation, pigmentation disorders, and circadian rhythm disruption, all of which accelerate photoaging. Despite growing interest, clinical awareness and protective strategies remain limited.
Methods: A systematic PubMed search was conducted for studies published between 2008 and 2025. Eligible publications included in vitro, in vivo, and clinical investigations assessing HEV-induced oxidative stress, deoxyribonucleic acid (DNA) damage, pigmentation, circadian rhythm alterations, and photoaging mechanisms. Interventions such as antioxidants, HEV-blocking sunscreens, and pigment-containing formulations were also evaluated. Data extraction and study selection were performed independently by all reviewers. Given heterogeneity of study designs and outcomes, results were synthesized narratively.
Results: In vitro studies demonstrated HEV-induced reactive oxygen species (ROS) generation, matrix metalloproteinase (MMP) activation, fibroblast proliferation impairment, and DNA damage, leading to collagen degradation and premature aging. Opsin-3-mediated melanogenesis contributed to hyperpigmentation. High-energy visible exposure disrupted circadian regulation and weakened antioxidant defenses. In vivo and clinical evidence showed alterations in skin biomechanics and fibroblast migration. Photoprotective formulations containing pigments and antioxidants reduced oxidative stress, MMP activity, and pigmentation, although study designs were small and short-term.
Conclusions: High-energy visible significantly affects skin physiology at multiple levels and contributes to photoaging and pigmentary disorders. Photoprotection should extend beyond UV filters to include HEV-targeted strategies. Standardized clinical trials are needed to establish exposure thresholds and optimize prevention
Causal relationship between peripheral immune cell phenotypes and recurrent miscarriage: a two-way Mendelian randomization analysis
No full textObjectives: Recurrent miscarriage is a multifactorial condition, with immune dysregulation proposed as a potential contributing factor. This study investigates the causal relationship between immune cell phenotypes and miscarriage risk using Mendelian randomization (MR). Material and methods: We performed a two-sample MR analysis using genome-wide association study (GWAS) summary statistics from publicly available datasets. The exposure data for immune cell phenotypes were obtained from the ebi-a-GCST90001599 dataset in the IEU GWAS database, which included over 3,000 individuals of predominantly European ancestry from multiple cohorts within the UK Biobank. The outcome data for miscarriage risk were sourced from the UKB-B-419 dataset in the MRC-IEU GWAS database, which analysed the number of spontaneous miscarriages in 78,700 individuals of predominantly European ancestry from the United Kingdom. The primary MR analysis was conducted using inverse-variance weighted (IVW) regression, complemented by Wald ratio and MR-Egger regression methods to assess robustness. MR-PRESSO was used to test for pleiotropy, while sensitivity analyses evaluated instrument validity and heterogeneity. Results: MR-Egger regression did not provide statistically significant evidence for a causal association between immune cell phenotypes and miscarriage risk. However, IVW and Wald ratio analyses identified statistically significant associations between specific immune cell profiles and miscarriage risk. A higher proportion of HLA DR+ CD4+ and CD8+ T cells was associated with an increased risk of miscarriage (p < 0.005), while a higher absolute lymphocyte count was linked to a decreased risk (p = 0.011). Additionally, elevated levels of TCRgd T cells and FSC-A on CD4+ T cells were potentially protective against miscarriage (p < 0.01). Conversely, lower proportions of granulocytes and FSC-A on myeloid dendritic cells were associated with an increased miscarriage risk (p < 0.05). MR-PRESSO detected significant pleiotropy (global test p < 0.001), suggesting that some genetic variants may influence other traits, potentially biasing the initial MR estimates. Conclusions: Our findings suggest a complex interplay between immune cell composition and miscarriage risk, providing new insights into the immunological mechanisms contributing to pregnancy loss. These results highlight the need for further research to confirm these associations and explore potential therapeutic targets for immune-related pregnancy complications
Does toxicity of cyclin-dependent kinase 4/6 inhibitor predict treatment response in metastatic hormone-positive breast cancer patients?
Full text linkIntroduction. In hormone receptor-positive metastatic breast cancer without human epidermal growth factor receptor 2 overexpression (HR+/HER2−), a significant progression-free survival benefit has been obtained with cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors in the first-line treatment. We mainly aimed to investigate whether the toxicities of CDK 4/6 inhibitors predict treatment response.
Material and methods. This study was designed retrospectively. A total of 191 patients diagnosed with metastatic HR+/HER2– breast cancer were treated with CDK 4/6 inhibitors in four centers in Türkiye included in our study.
Results. One hundred and six patients received ribociclib, and 85 patients received palbociclib. The most common adverse event in both groups was neutropenia. In this study, we found that toxicities did not predict response rates.
Additionally, the response rates (RR) in patients with albumin levels above 4.1 g/dl were better than that in patients with albumin levels of 4.1 g/dL and below in multivariate analysis when all patients were considered (OR = 4.76; 95% CI 1.30–17.46; p = 0.018).
Conclusions. Toxicities of CDK4/6-inhibitors did not predict RRs. However, pretreatment albumin level may predict response to ribociclib